MCID: LKD010
MIFTS: 41

Leukodystrophy, Hypomyelinating, 2

Categories: Genetic diseases, Neuronal diseases, Rare diseases, Eye diseases

Aliases & Classifications for Leukodystrophy, Hypomyelinating, 2

MalaCards integrated aliases for Leukodystrophy, Hypomyelinating, 2:

Name: Leukodystrophy, Hypomyelinating, 2 54 71 29 13 69
Pmld1 12 24 56 71
Hypomyelinating Leukodystrophy 2 12 24 14
Hld2 12 24 71
Pelizaeus-Merzbacher-Like Disease Due to Gjc2 Mutation 12 56
Pelizaeus-Merzbacher-Like Disease 1 12 24
Pelizaeus-Merzbacher-Like Disease Autosomal Recessive Type 1 71
Pelizaeus-Merzbacher-Like Disease Type 1 71
Pmldar1 71

Characteristics:

Orphanet epidemiological data:

56
pelizaeus-merzbacher-like disease due to gjc2 mutation
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal;

OMIM:

54
Inheritance:
autosomal recessive

Miscellaneous:
onset in infancy
most children become wheelchair-bound
similar disorder to x-linked pelizaeus-merzbacher disease (pmd, )


HPO:

32
leukodystrophy, hypomyelinating, 2:
Onset and clinical course infantile onset
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 56  
Rare neurological diseases


Summaries for Leukodystrophy, Hypomyelinating, 2

Disease Ontology : 12 A hypomyelinating leukodystrophy characterized by autosomal recessive inheritance of nystagmus, impaired motor development, ataxia, choreoathetotic movements, dysarthria, and progressive spasticity that has material basis in homozygous or compound heterozygous mutation in the GJC2 gene on chromosome 1q42.

MalaCards based summary : Leukodystrophy, Hypomyelinating, 2, also known as pmld1, is related to mental retardation, x-linked, syndromic 34 and spastic ataxia 3, autosomal recessive, and has symptoms including optic atrophy, dystonia and dysarthria. An important gene associated with Leukodystrophy, Hypomyelinating, 2 is GJC2 (Gap Junction Protein Gamma 2), and among its related pathways/superpathways are Neural Crest Differentiation and Glial Cell Differentiation. Related phenotypes are behavior/neurological and cellular

UniProtKB/Swiss-Prot : 71 Leukodystrophy, hypomyelinating, 2: An autosomal recessive hypomyelinating leukodystrophy with symptoms of Pelizaeus-Merzbacher disease. Clinically characterized by nystagmus, impaired motor development, ataxia, choreoathetotic movements, dysarthria, and progressive spasticity.

Description from OMIM: 608804

Related Diseases for Leukodystrophy, Hypomyelinating, 2

Diseases in the Hypomyelinating Leukodystrophy family:

Leukodystrophy, Hypomyelinating, 2 Leukodystrophy, Hypomyelinating, 10
Leukodystrophy, Hypomyelinating, 4 Leukodystrophy, Hypomyelinating, 3
Leukodystrophy, Hypomyelinating, 9 Leukodystrophy, Hypomyelinating, 11
Leukodystrophy, Hypomyelinating, 5 Leukodystrophy, Hypomyelinating, 13
Leukodystrophy, Hypomyelinating, 12 Leukodystrophy, Hypomyelinating, 6

Diseases related to Leukodystrophy, Hypomyelinating, 2 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 43)
id Related Disease Score Top Affiliating Genes
1 mental retardation, x-linked, syndromic 34 10.7 GJB1 GJC2
2 spastic ataxia 3, autosomal recessive 10.7 GJC2 PLP1
3 cerebellar ataxia, mental retardation and dysequlibrium syndrome 10.7 GJC2 PLP1
4 phosphoribosylpyrophosphate synthetase superactivity 10.6 GJC2 PLP1
5 glucose/galactose malabsorption 10.6 FA2H PANK2
6 prieto syndrome 10.5 GJB1 GJC2 PLP1
7 alopecia intellectual disability syndrome 2 10.4 MBP PLP1
8 sclerosing keratitis 10.4 FA2H GJC2 PLP1
9 naegeli-franceschetti-jadassohn syndrome 10.4 PANK2 VPS13A
10 pre-eclampsia 10.4 FA2H GJC2 PLP1
11 herpes simplex encephalitis 7 10.4 FA2H JPH3 PANK2
12 niemann-pick disease, type b 10.4 MBP PLP1
13 cranio-facial dystonia 10.3 GCH1 TOR1A
14 granulomatous angiitis 10.3 PLP1 TOR1A
15 cervical dystonia 10.3 GCH1 TOR1A
16 eccentrochondrodysplasia 10.3 GCH1 TOR1A
17 hereditary spastic paraplegia 3a 10.3 FA2H PANK2 VPS13A
18 pemphigoid gestationis 10.3 GJB1 GJC2 PLP1 SNAP29
19 oromandibular dystonia 10.3 PANK2 TOR1A
20 hallux varus and preaxial polysyndactyly 10.3 GJB1 GJC2
21 intestinal disease 10.2 GCH1 TOR1A
22 mohr-tranebjaerg syndrome 10.2 GJC2 MBP PLP1
23 specific language impairment 5 10.2 GCH1 TOR1A
24 parkinson disease 14, autosomal recessive 10.2 FA2H PANK2
25 hypoxia 10.2 GJB1 MBP PLP1
26 hyperphenylalaninemia, bh4-deficient, b 10.2 GCH1 TOR1A
27 neuropathy, recurrent, with pressure palsies 10.2 GJB1 MBP
28 pelizaeus-merzbacher disease 10.1
29 pelizaeus-merzbacher-like disease 10.1
30 sleep apnea 10.1 GCH1 GJC2 TOR1A
31 amyloidosis, finnish type 10.1 GCH1 TOR1A
32 tuberculosis 10.1 GCH1 GJC2 TOR1A
33 uv-induced skin damage 10.1 HTT JPH3
34 oculogyric crisis 10.1 GCH1 TOR1A
35 corneal endothelial dystrophy, autosomal recessive 10.1 FA2H JPH3 PANK2 VPS13A
36 obstructive sleep apnea 10.0 GCH1 TOR1A
37 alternating hemiplegia of childhood 2 10.0 GCH1 PANK2 TOR1A
38 epilepsy, familial temporal lobe, 4 9.9 HCCS JPH3 PANK2 VPS13A
39 sjogren's syndrome 9.9 HTT JPH3 VPS13A
40 scrapie 9.7 FA2H GCH1 PANK2 TOR1A
41 long qt syndrome-11 9.7 GCH1 TOR1A
42 hepatic angiomyolipoma 9.5 HTT MBP PLP1
43 ganglioneuroma 9.2 GCH1 HTT PANK2 TOR1A

Graphical network of the top 20 diseases related to Leukodystrophy, Hypomyelinating, 2:



Diseases related to Leukodystrophy, Hypomyelinating, 2

Symptoms & Phenotypes for Leukodystrophy, Hypomyelinating, 2

Symptoms via clinical synopsis from OMIM:

54

Head And Neck- Face:
facial weakness

Head And Neck- Eyes:
optic atrophy
myopia
rotary nystagmus

Neurologic- Peripheral Nervous System:
peripheral neuropathy, mild (less common)
decreased motor nerve conduction velocities (ncv)
demyelinating motor neuropathy
axonal sensory neuropathy

Neurologic- Central Nervous System:
delayed psychomotor development
dystonia
dysarthria
ataxia
lack of independent ambulation
more
Head And Neck- Head:
head titubation


Clinical features from OMIM:

608804

Human phenotypes related to Leukodystrophy, Hypomyelinating, 2:

32 (show all 26)
id Description HPO Frequency HPO Source Accession
1 optic atrophy 32 HP:0000648
2 dystonia 32 HP:0001332
3 dysarthria 32 HP:0001260
4 ataxia 32 HP:0001251
5 myopia 32 HP:0000545
6 choreoathetosis 32 HP:0001266
7 cognitive impairment 32 HP:0100543
8 cerebral atrophy 32 HP:0002059
9 seizures 32 HP:0001250
10 global developmental delay 32 HP:0001263
11 rigidity 32 HP:0002063
12 poor speech 32 HP:0002465
13 motor delay 32 HP:0001270
14 spastic paraparesis 32 HP:0002313
15 leukodystrophy 32 HP:0002415
16 head titubation 32 HP:0002599
17 rotary nystagmus 32 HP:0001583
18 demyelinating motor neuropathy 32 HP:0007220
19 intention tremor 32 HP:0002080
20 babinski sign 32 HP:0003487
21 facial palsy 32 HP:0010628
22 sensory axonal neuropathy 32 HP:0003390
23 progressive spasticity 32 HP:0002191
24 decreased motor nerve conduction velocity 32 HP:0003431
25 muscular hypotonia of the trunk 32 HP:0008936
26 cerebral hypomyelination 32 HP:0006808

UMLS symptoms related to Leukodystrophy, Hypomyelinating, 2:


ataxia, muscle rigidity, seizures, paraparesis, spastic, action tremor, facial paresis, head titubation

MGI Mouse Phenotypes related to Leukodystrophy, Hypomyelinating, 2:

44
id Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 10.29 DLL1 FA2H GJB1 GJC2 HTT JPH3
2 cellular MP:0005384 10.2 MBP NRAS PANK2 PLP1 SNAP29 TOR1A
3 growth/size/body region MP:0005378 10.17 HTT JPH3 MBP NRAS PANK2 PLP1
4 homeostasis/metabolism MP:0005376 10.11 DLL1 FA2H GJB1 HCCS HTT MBP
5 hematopoietic system MP:0005397 10.06 DLL1 GJB1 GJC2 HTT MBP NRAS
6 mortality/aging MP:0010768 10.03 DLL1 GJB1 GJC2 HCCS HTT JPH3
7 immune system MP:0005387 9.92 DLL1 GJB1 GJC2 HTT MBP NRAS
8 nervous system MP:0003631 9.9 DLL1 FA2H GJB1 GJC2 HTT JPH3
9 normal MP:0002873 9.5 MBP NRAS TOR1A DLL1 GJC2 HCCS
10 vision/eye MP:0005391 9.23 FA2H GJB1 GJC2 MBP NRAS PANK2

Drugs & Therapeutics for Leukodystrophy, Hypomyelinating, 2

Search Clinical Trials , NIH Clinical Center for Leukodystrophy, Hypomyelinating, 2

Genetic Tests for Leukodystrophy, Hypomyelinating, 2

Genetic tests related to Leukodystrophy, Hypomyelinating, 2:

id Genetic test Affiliating Genes
1 Leukodystrophy, Hypomyelinating, 2 29
2 Pelizaeus-Merzbacher-Like Disease 1 24 GJC2

Anatomical Context for Leukodystrophy, Hypomyelinating, 2

Publications for Leukodystrophy, Hypomyelinating, 2

Variations for Leukodystrophy, Hypomyelinating, 2

UniProtKB/Swiss-Prot genetic disease variations for Leukodystrophy, Hypomyelinating, 2:

71
id Symbol AA change Variation ID SNP ID
1 GJC2 p.Pro90Ser VAR_023754 rs74315312
2 GJC2 p.Tyr272Asp VAR_023755 rs74315314
3 GJC2 p.Met286Thr VAR_023756 rs74315311

ClinVar genetic disease variations for Leukodystrophy, Hypomyelinating, 2:

6 (show all 14)
id Gene Variation Type Significance SNP ID Assembly Location
1 GJC2 NM_020435.3(GJC2): c.857T> C (p.Met286Thr) single nucleotide variant Pathogenic rs74315311 GRCh37 Chromosome 1, 228346316: 228346316
2 GJC2 NM_020435.3(GJC2): c.268C> T (p.Pro90Ser) single nucleotide variant Pathogenic rs74315312 GRCh37 Chromosome 1, 228345727: 228345727
3 GJC2 NM_020435.3(GJC2): c.989delC (p.Pro330Argfs) deletion Pathogenic rs796065027 GRCh38 Chromosome 1, 228158747: 228158747
4 GJC2 NM_020435.3(GJC2): c.718C> T (p.Arg240Ter) single nucleotide variant Pathogenic rs74315313 GRCh37 Chromosome 1, 228346177: 228346177
5 GJC2 NM_020435.3(GJC2): c.814T> G (p.Tyr272Asp) single nucleotide variant Pathogenic rs74315314 GRCh37 Chromosome 1, 228346273: 228346273
6 GJC2 NM_020435.3(GJC2): c.914_947del34 (p.Pro305Argfs) deletion Pathogenic rs796065028 GRCh38 Chromosome 1, 228158672: 228158705
7 GJC2 NM_020435.3(GJC2): c.695_696insG (p.Tyr232Terfs) insertion Pathogenic rs796065029 GRCh38 Chromosome 1, 228158453: 228158454
8 GJC2 NM_020435.3(GJC2): c.-167A> G single nucleotide variant Pathogenic rs587776888 GRCh37 Chromosome 1, 228337561: 228337561
9 GJC2 NM_020435.3(GJC2): c.787G> A (p.Glu263Lys) single nucleotide variant Pathogenic rs397514734 GRCh37 Chromosome 1, 228346246: 228346246
10 GJC2 NM_020435.3(GJC2): c.-170A> G single nucleotide variant Pathogenic rs587777496 GRCh37 Chromosome 1, 228337558: 228337558
11 GJC2 NM_020435.3(GJC2): c.78delG (p.Trp27Glyfs) deletion Likely pathogenic rs886039904 GRCh37 Chromosome 1, 228345537: 228345537
12 SNAP29 NM_004782.3(SNAP29): c.2T> C (p.Met1Thr) single nucleotide variant Pathogenic rs886041240 GRCh37 Chromosome 22, 21213400: 21213400
13 SNAP29 NM_004782.3(SNAP29): c.354dupG (p.Leu119Alafs) duplication Pathogenic rs886041263 GRCh37 Chromosome 22, 21224741: 21224741
14 GJC2 NM_020435.3(GJC2): c.1175C> G (p.Ser392Cys) single nucleotide variant Likely pathogenic GRCh37 Chromosome 1, 228346634: 228346634

Expression for Leukodystrophy, Hypomyelinating, 2

Search GEO for disease gene expression data for Leukodystrophy, Hypomyelinating, 2.

Pathways for Leukodystrophy, Hypomyelinating, 2

Pathways related to Leukodystrophy, Hypomyelinating, 2 according to GeneCards Suite gene sharing:

id Super pathways Score Top Affiliating Genes
1 11.14 DLL1 GJB1 MBP
2 9.53 MBP PLP1

GO Terms for Leukodystrophy, Hypomyelinating, 2

Cellular components related to Leukodystrophy, Hypomyelinating, 2 according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 gap junction GO:0005921 9.16 GJB1 GJC2
2 myelin sheath GO:0043209 9.13 GJC2 MBP PLP1
3 connexin complex GO:0005922 8.62 GJB1 GJC2

Biological processes related to Leukodystrophy, Hypomyelinating, 2 according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 astrocyte development GO:0014002 9.16 DLL1 PLP1
2 axon ensheathment GO:0008366 8.96 MBP PLP1
3 cell communication GO:0007154 8.8 DLL1 GJB1 GJC2

Molecular functions related to Leukodystrophy, Hypomyelinating, 2 according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 structural constituent of myelin sheath GO:0019911 8.62 MBP PLP1

Sources for Leukodystrophy, Hypomyelinating, 2

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
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48 NDF-RT
51 NINDS
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54 OMIM
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59 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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